Mental retardation is defined as sub-normal intellect and impaired adaptive functioning. The Intelligence Quotient (IQ) distribution across the population is normal, with an average of 100 points. Mental retardation is defined as an IQ of less than 70 points. As can be expected, a range of severity exists for the condition, with mild mental retardation being defined as an IQ of 50-70, moderate mental retardation being equivalent to an IQ of 35-49, while profound mental retardation as categorized as having an IQ of less than 20 points. The etiology of mental retardation is varied. In a large number of cases, the condition is X-linked, but not associated with Fragile X syndrome. These cases are classified as non-specific X linked Mental Retardation (XLMR). To date more than 80 different types of XLMR have been identified, each one linked to a different genetic locus.

Diagnosis of XLMR requires an exclusion of other causes of cognitive delay. This includes karyotypic analysis for any chromosomal defects, including submicroscopic telomeric deletions, fragile X, or autosomal translocations. There is no cure for this disability. Management is supportive, with an emphasis on occupational and behavioral therapy.

According to one estimate, there are about 200 genes involved in different forms of X-linked mental Retardation, of which about 100 have been identified. XLMR1 was the first subtype of the condition to be positively associated with a genetic locus. It was later found that this locus contained the IQ Motif- and SEC7 Domain-Containing Protein 2 (IQSEC2) gene, which codes for a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. Mutations in this gene have been identified in patients with XLMR1. The IQSEC2 protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates.